Halogenated dibenzofurans are found worldwide as environmental pollutants. Structurally related to other halogenated aromatic xenobiotics, their toxicity and disposition seem to vary with the degree and position of halogenation. This work has established that 2,3,7,8-tetrachlorodibenzofuran (TCDF), an extremely toxic isomer, is excreted only after metabolism and toxicity is inversely related to metabolic capability. The concept of a threshold body burden for toxicity is currently being tested. The distribution to the fetus will be examined after maternal exposure. The role of body composition on the disposition of 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the most toxic man-made compound known, is being examined in congenic mouse strains which are sensitive or resistant to TCDD toxicity.